Fluoride-induced apoptosis and gene expression profiling in mice sperm in vivo
Fluoride-induced apoptosis and gene expression profiling in mice sperm in vivo
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DOI：
10.1007/s00204-011-0672-7
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发表时间：
2011-02
影响因子：
6.1
通讯作者：
Zilong Sun;R. Niu;Bin Wang;Zhibin Jiao;Jinming Wang;Jianhai Zhang;Shaolin Wang;Jundong Wang
中科院分区：
文献类型：
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作者：
Zilong Sun;R. Niu;Bin Wang;Zhibin Jiao;Jinming Wang;Jianhai Zhang;Shaolin Wang;Jundong Wang
暴露于氟化物可导致精子质量低下;然而，人们对氟化物发挥其毒性作用的分子机制知之甚少。本研究旨在评价用150 mg/l NaF处理49天的小鼠精子的超微结构、氧化应激和细胞凋亡。此外，还利用微阵列分析来表征氟对小鼠精子基因表达谱的影响。氟组小鼠精子中活性氧含量增加，总抗氧化能力降低，精子形态学改变明显，凋亡细胞明显。氟暴露还显著提高细胞色素c和活性caspase-3的蛋白表达。在基因表达谱分析中，34个上调基因和63个下调基因表达差异显著，这些基因涉及精子的信号转导、氧化应激、细胞凋亡、电子传递、糖酵解、趋化性、精子发生和精子获能等生物学过程。基于这些发现，有人提出，过量ROS诱导的氧化应激可能通过线粒体损伤引发精子凋亡，导致暴露于氟化物的小鼠生育力下降。微阵列分析也为进一步研究氟对精子形态和功能的损伤提供了重要的生物学线索。
Exposure to fluoride can induce low sperm quality; however, little is known about the molecular mechanisms by which fluoride exerts its toxic effects. This study was conducted to evaluate ultrastructure, oxidative stress, and apoptosis in sperm of mice treated with 150 mg/l NaF for 49 days. Furthermore, microarray analysis was also utilized to characterize the effects of fluoride in gene expression profiling on mice sperm. An increased ROS and a decreased TAC accompanied with distinct morphological changes and significant apoptosis were observed in mice sperm from the fluoride group. Fluoride exposure also significantly elevated the protein expressions of cytochrome c and active caspase-3. In global gene expression profiling, 34 up-regulated and 63 down-regulated genes, which are involved in several sperm biological processes including signal transduction, oxidative stress, apoptosis, electron transport, glycolysis, chemotaxis, spermatogenesis, and sperm capacitation, were significantly differentially expressed. Based on these findings, it was proposed that oxidative stress induced by excessive ROS may trigger sperm apoptosis through mitochondrial impairment, resulting in decreased fertility in mice exposed to fluoride. Microarray analysis also provided several important biological clues for further investigating fluoride-induced damage in sperm morphology and functions.